We propose to study the effects of hypoxia on cerebral blood flow (QC) in the fetus, newborn and adult. Hypoxia can be produced in several ways, by lowering the PO2 (hypoxic hypoxia) or the hematocrit (anemic hypoxia) and by administration of carbon monoxide (CO hypoxia). All cause an increase in QC. We hypothesize that the rise in QC in each of these situations is in reciprocal relationship to the fall in arterial oxygen content (CaO2) so that oxygen delivery (QC x CaO2) is constant. This occurs independently of changes in arterial or cerebral venous PQ2. Thus, regulation of QC during hypoxia in the fetus, with a low PO2, would be essentially the same as in the newborn and adult. Cerebral oxygen consumption (VO2C) is not affected by change in CaO2, thus the ratio VO2C/(QC x CaO2), i.e. the percentage extraction of oxygen, should also be constant. This ratio is equal to the "extraction coefficient", (a-v)/CaO2, where (a-v) is the cerebral arteriovenous oxygen difference. We will measure QC and (a-v)/CaO2 in the three types of hypoxia in unanesthetized fetal, newborn and adult sheep. Qc will be measured with radioactive microspheres and (a-v) will be measured between the brachiocephalic artery and the superior sagittal sinus. If we confirm that (QC x CaO2) is constant in relationship to VO2C, a local mechanism of blood flow regulation is implicated. We will therefore examine the role of tissue oxygenases in the regulation of QC. Finally, we will assess the importance of blood pressure to the regultion of QC during hypoxia.